Calcium Manganese Titanium oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 May - 20 July 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted to international guideline and under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Regulation on Test Methods for Chemical Substances” Notification No. 2018-12, National Institute of Environmental Research, Republic of Korea

Version / remarks:

2018

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

- Storage condition of test material: At room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

(Crl:CD(SD)),SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ORIENTBIOINC.,RepublicofKorea
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 163.4 - 196.9 g
- Fasting period before study: yes
- Housing: Animals were individually housed in Stainless wire mesh cage, 260W×350D×210H (mm), One animal/cage (during the study).
- Diet (e.g. ad libitum): Pelleted rodent chow
(Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C, Lot no. 2918C-012918MA) placed in feeders and provided ad libitum. 
- Water (e.g. ad libitum): Public tap water in Cheongju-si was filtered and irradiated by ultraviolet light and provided ad libitum. 

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0−25.0°C
- Humidity (%): 30.0−70.0%
- Air changes (per hr): 10−15 clean, fresh, filtered air changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12
IN-LIFE DATES: 23/5/ 2018 - 12 and 15 June 2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Oral via gastric intubation

Details on oral exposure:

Individual doses were calculated based on the animals’ body weight recorded just prior to dosing at a dose volume of 10 mL/kg body weight. Animals were dosed via gastric intubation with a 3-mL disposable syringe fitted with an intubation tube. Animals were fasted overnight, approximately 16 hours prior to dosing. Drinking water was provided ad libitum. Feed was provided approximately 4 hours after dosing.

Doses:

2,000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

Due to the low expected toxicity of the test substance, 2,000 mg/kg was selected as the starting dose. A dose of 2,000 mg/kg was administered to three females. Based on observation of no mortality,a second dose of 2,000 mg/kg was administered to another set of 3 female.

Statistics:

Not required but mean scores and values were determined.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No adverse effects observed

Mortality:

No deaths reported

Clinical signs:

other: Compound-colored stool was observed in all animals at 2,000 mg/kg on Day 1 after dosing. Then, these animals returned to a normal appearance on Day 2 after dosing.

Gross pathology:

No grossly visible abnormalities were observed in any animal at 2,000 mg/kg.

Other findings:

None

Any other information on results incl. tables

Table 2. Mean Body Weights

Step / Dose(mg/kg)	Days after dosing
	0	1	3	7	14	Gain (g)0∼14
Step 1  2,000	174.1	190.6	200.2	209.8	235.7	61.6
Step 1  2,000	186.5	208.7	221.1	229.6	246.4	59.9

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System).

Executive summary:

OECD 423 (2018) - In an acute oral toxicity study, a group of  7-8 week old female Wistar rats were given a single oral dose of the test item using a stepwise dose rate of 2000 mg/kg bw and observed for 14 days.

In the absence of mortality during the observation period, the oral LD50 was estimated to be > 2000 mg/kg bw.

Compound-coloured stool was observed in animals on Day 1. This change disappeared on Day 2. No test substance-related effects were observed in the body weight data or necropsy findings in any animal at 2,000 mg/kg.

In conclusion, the test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.